1-157580343-C-T

Variant names:

• chr1-157580343-C-T
• NM_031282.3:c.1255G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031282.3(FCRL4):​c.1255G>A​(p.Gly419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G419C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

Genes affected

FCRL4 (HGNC:18507): (Fc receptor like 4) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL4	NM_031282.3	c.1255G>A	p.Gly419Ser	missense_variant	Exon 8 of 12	ENST00000271532.2	NP_112572.1
FCRL4	XM_011510034.2	c.1252G>A	p.Gly418Ser	missense_variant	Exon 8 of 12		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL4	ENST00000271532.2	c.1255G>A	p.Gly419Ser	missense_variant	Exon 8 of 12	1	NM_031282.3	ENSP00000271532.1
FCRL4	ENST00000448509.6	n.996G>A		non_coding_transcript_exon_variant	Exon 6 of 9	2
FCRL4	ENST00000479869.1	n.195G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.65
DANN	Benign	0.84
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.018
Sift	Benign	0.48	T
Sift4G	Benign	0.24	T
Polyphen		0.29	B
Vest4		0.18
MutPred		0.34		Loss of sheet (P = 0.0315);
MVP		0.15
MPC		0.033
ClinPred		0.055	T
GERP RS		-0.090
Varity_R		0.027
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-157550133;